Autoimmune
alopecia (
alopecia areata) is considered to be triggered by a collapse of immune privilege in hair follicles. Here we confirmed that infiltrating CD4 T lymphocytes around hair follicles of patients with
alopecia areata were primarily CCR5-positive with few CCR4-positive cells, suggesting a dominant role of Th1 cells in the alopecic lesion. Given this finding, we sought to elucidate the effect of
cytokine therapy in C3H/HeJ mice, a mouse model of
alopecia areata, by applying recombinant
interleukin-4 and neutralizing anti-
interferon-gamma antibody. We found that local
injections of both
interleukin-4 and neutralizing anti-
interferon-gamma antibody effectively treated
alopecia in C3H/HeJ mice. Results from immunohistochemistry and semiquantitative reverse transcription-polymerase chain reaction demonstrated that
intralesional injection of
interleukin-4 suppressed CD8 T cell infiltrates around the hair follicles and repressed enhanced
interferon-gamma mRNA expression in the affected alopecic skin. Furthermore, Th1
transcription factor T-box21 small interfering RNAs conjugated to cationized
gelatin showed mitigating effects on
alopecia in C3H/HeJ mice, resulting in the restoration of hair shaft elongation. Taken together, the use of
gelatin-
small interfering RNA conjugates promises to be a novel, efficient, and safe tool as an alternative gene therapy for the treatment of various human diseases. To our knowledge, this is the first report of effective controlled delivery of
small interfering RNA using biodegradable cationized
gelatin microspheres in an animal model of disease.